CAREER: Illuminating Emergent Microbial Interactions via Modular Synthetic Consortia

微生物群落对人类健康和生物技术具有重要作用。两个例子是与人体相关的许多微生物（例如，肠道微生物组）和有助于土壤肥力和植物健康的物种。这些含有许多不同物种的天然微生物聚生体通常由特征较差的微生物组成。它们也有复杂的化合物和代谢物信号网络，在群落成员之间交换。自然财团的复杂性使其难以研究，并可能使许多不同社区所依据的共同原则难以确定。因此，许多基本问题仍然是关于微生物聚生体如何组织起来以在动态环境条件下保持生产力和恢复力。该项目利用相对简单且由特征良好的微生物组成的人工微生物群落。选择人工群落的这些特征是为了促进调查，从而深入了解指导微生物群落结构和功能的基本原则。这些研究活动增加了对微生物群落相互作用动力学的了解，有可能提高设计微生物联合体的能力。这项研究还提供了对自然微生物共生体进化的见解。通过该项目，培养了两名研究生和一名博士后研究员。此外，还有多个本科研究经验的机会。该项目还涉及促进发展公共论坛，讨论生物工程的潜在好处和伦理问题。这些论坛在底特律的密歇根科学中心举办。研究小组使用的是一种蓝细菌（细长聚球藻PCC 7942），它能从光线和二氧化碳中产生并分泌大量蔗糖。PI已经证明，多种其他微生物可以以“模块化”方式在相同的培养基中培养。在这些情况下，共培养的伴侣消耗蓝细菌产生的蔗糖。这些人工微生物群落设计的灵活性允许不同的异养细菌与蓝细菌一起培养。通过这种方式，共同培养的物种之间的相互作用的共同主题和机制被确定。包括理性工程、正向遗传学、定向进化、代谢建模和基于个体的模拟在内的方法被用来识别物种之间交换的代谢物和信号。这些方法也用于确定代谢物交换如何有助于聚生体稳健性。所获得的知识用于合理设计微生物群落，使其在面对环境压力时更加强大，例如“非合作”微生物物种的入侵。预计该提案的研究成果将为自然微生物共生的基础相互作用提供深入的见解，并对环境可持续的蓝藻生物技术的发展产生转化影响。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Microbial communities contribute important functions towards human health and biotechnology. Two examples are the many microbes associated with the human body (e.g., gut microbiome) and species that contribute to soil fertility and plant health. These natural microbial consortia that contain many different species, are often composed of poorly-characterized microbes. They also have complicated signaling networks of compounds and metabolites that are exchanged between community members. The complexity of natural consortia makes them difficult to study and can obscure identification of common principles that underlie many different communities. Consequently, many fundamental questions remain about how microbial consortia are organized to maintain productivity and resilience in the face of dynamic environmental conditions. This project makes use of artificial microbial communities that are relatively simple and composed of well-characterized microbes. These features of the artificial communities are chosen to facilitate an investigation that would lead to insight into underlying principles that guide the structure and function of microbial communities. The research activities increase knowledge of interaction dynamics in microbial communities, potentially improving the ability to engineer microbial consortia. The research also provides insight into the evolution of natural microbial symbioses. Through this project two graduate students and one postdoctoral fellow are trained. In addition, there are multiple undergraduate research experience opportunities. The project also involves promoting the development of public forums for the discussion of potential benefits and ethical concerns of bioengineering. These forums are hosted in the Michigan Science Center in Detroit.The research team is using a cyanobacterium (Synechococcus elongatus PCC 7942) that produces and secretes large quantities of sucrose from light and CO2. The PI has demonstrated that a variety of other microbes can be cultivated in the same media in a "modular" fashion. In these circumstances the co-cultured partner consumes the sucrose produced by the cyanobacteria. The flexibility in the design of these artificial microbial communities allows different heterotrophic bacteria to be cultivated with the cyanobacterium. In this way, common themes and mechanisms of interaction between the co-cultured species are identified. Approaches that include rational engineering, forward genetics, directed evolution, metabolic modeling, and individual-based simulations are used to identify the metabolites and signals exchanged between species. These approaches are also used to determine how metabolite exchanges contribute to consortia robustness. The knowledge gained is used to rationally design microbial communities that are more robust in the face of environmental pressures, such as invasion by "non-cooperating" microbial species. It is anticipated that the research efforts from this proposal will provide insights into fundamental interactions underpinning natural microbial symbioses, with translational impacts for the development of environmentally-sustainable cyanobacterial biotechnologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.